Prospectively collected Surveillance Epidemiology and End Results (SEER) data indicate that the incidence of esophageal adenocarcinoma (EAC) has increased more than 5-fold in the past three decades. Over 10,000 cases are now diagnosed annually. The prognosis for patients with EAC is poor with less than 20% of patients surviving beyond 5 years.
Barrett's esophagus (BE), a pre-malignant metaplastic condition that is the only known precursor of EAC, is diagnosed when patients undergo upper endoscopy (EGD) often for symptoms of gastroesophageal reflux disease (GERD). Once BE has been diagnosed, subsequent surveillance with periodic EGD is the current strategy for the early detection of dysplasia/cancer. However, most patients with BE do not progress to EAC and surveillance may or may not result in improved survival. Thus, it is imperative to develop surveillance strategies that target only the selected few with the greatest risk of progression to dysplasia and cancer and stop surveying those with no risk of progression.
Endoscopic surveillance strategies are based on the identification of dysplasia in random biopsies. Poor agreement among pathologists in interpreting dysplasia and the reliance of this strategy on random endoscopic biopsies, which sample only a small fraction of the BE segment are two major factors that explain why surveillance is ineffective. Robust molecular markers that predict the progression of BE to EAC would improve the efficacy of surveillance by enabling a more robust diagnosis of dysplasia, especially if the markers were applied to endoscopic brushings obtained from the entire segment of BE.
Patients with BE who are diagnosed with high grade dysplasia or low grade dysplasia can be treated with endoscopic ablation. Ablative therapies can prevent the progression of BE to cancer. However, some patients who undergo ablation may still develop cancer. Therefore, these patients need to be followed closely. Molecular markers that can identify dysplasia and risk of progression to cancer would guide ablative therapies and would be useful in following these patients after ablation.
The final challenge lies in patients who develop EAC. The prognosis of these patients is poor because the majority of them develop invasive metastatic cancer. These patients are often treated with concurrent chemotherapy and radiation therapy. Cis-platin plus 5-FU combination chemotherapy, the most commonly used regimen, has a response rate of less than 50% in EAC patients. Other regimens based around taxanes or irinotecan also have similar response rates. Molecular markers that can guide the selection of chemotherapy or radiation therapy regimens and predict which cancers will respond would improve the treatment of EAC patients. Moreover, development of new evidence-based therapeutic targets would significantly aid in the treatment of advanced EACs, and in preventing disease recurrence or metastatic spread, and in the overall management of the disease.